DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1-6, 8-11, 13, 14 and 16-18 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Broughton et al (WO 2020/257356). Regarding Claim 1, Broughton et al teaches a pathogen nucleic acid detection system (see abstract), comprising, in fluid communication, a recombinase polymerase amplification (RPA) reaction chamber (referred to as an amplification reagent chamber, containing an amplification reagent such as a recombinase polymerase, see [0022], [0027] and [0381]) for producing RPA amplification products comprising reagents for multiplex amplification of one or more target pathogen nucleic acids ([0318] and [0364]) and optionally a positive/negative control (wherein a positive control is disclosed in [0326] and a negative control is disclosed in [0720]), a microfluidic chip (referred to as a microfluidic cartridge, illustrated in Figures 46, 130A and 157) comprising a multiplexed detection chamber (one of the series of detection chambers 122) wherein each detection chamber comprises a cleavable nucleic acid probe and reagents (see [0003], [0442], [0500] and [0594]), the reagents comprising a CRISPR/Cas12a enzyme (see [0449] and [0457]), and a guide RNA (gRNA) specific for one target pathogen nucleic acid of the one or more target pathogen nucleic acids or for the positive/negative control (see [0364] and [0500]), and a valve (shown in Figure 157) controlling flow of the RPA amplification products from the RPA reaction chamber to the microfluidic chip, wherein, in a closed position, the valve stops the passage of the RPA amplification products to the microfluidic chip, and wherein the valve, in an open position, provides passage of the RPA amplification products to the microfluidic chip to initiate CRISPR/Cas12a nonspecific cleavage of the cleavable nucleic acid probe, wherein a detectable signal is generated in the detection chambers when the cleavable nucleic acid probe is cleaved by the CRISPR/Cas (see [0158], [0501], [0526] and [0880]) and wherein the detectable signal indicates the presence of the one or more target pathogen nucleic acids or positive/negative control (see [0319]-[0320] and [0326]).
Furthermore, examiner Wecker notes that claim 1 is an apparatus claims and while features of an apparatus may be recited either structurally or functionally (see In re Schreiber, 128 F.3d 1473, 1478, 44 USPQ2d 1429, 1432 (Fed. Cir. 1997), MPEP 2114), "[A]pparatus claims cover what a device is, not what a device does." Hewlett-Packard Co. v. Bausch & Lomb Inc., 909 F.2d 1464, 1469, 15 USPQ2d 1525, 1528 (Fed. Cir. 1990) (emphasis in original). See MPEP 2114.
Regarding Claim 2, Broughton et al teaches that the cleavable nucleic acid probe is a fluorophore-quencher-labeled ssDNA probe (see [0033], [0320] and [0721]).
Regarding Claim 3, Broughton et al teaches that the multiplexed detection chamber is a multiplexed paper detection chamber (where the detection pad may be constructed of paper) (see [0426] and [0706]).
Regarding Claim 4, Broughton et al teaches that the reagents in the multiplexed detection chamber are lyophilized (see [0379]-[0380] and [0519]).
Regarding Claim 5, Broughton et al teaches that the pathogen nucleic acid is from SARS- CoV-2 (see [0030] and [0534]).
Regarding Claim 6, Broughton et al teaches that the SARS-CoV-2 nucleic acid is an N gene (see [0030]).
Regarding Claim 8, Broughton et al teaches that the valve is a sucrose-based valve (see [0495] and [0579]).
Regarding Claim 9, Broughton et al teaches that the system further comprises a sample-collecting component (such as a buccal or nasal swab) that is a self-administered sample-collecting component (see [0524]).
Regarding Claim 10, Broughton et al teaches that each component of the detection system is stable at room temperature (see [0546]-[0547).
Regarding Claim 11, Broughton et al teaches that a detectable signal is generated after 40 minutes of incubation (since the sample is allowed to incubate in the amplification chamber for from 5 minutes to 40 minutes) (see [0500]). In addition, Broughton et al further discloses that In some cases, the devices, systems, fluidic devices, kits, and methods described herein detect a target single-stranded nucleic acid in a sample where the sample is contacted with the reagents for no greater than 60 minutes. Sometimes the sample is contacted with the reagents for no greater than 120 minutes, 110 minutes, 100 minutes, 90 minutes, 80 minutes, 70 minutes, 60 minutes, 55 minutes, 50 minutes, 45 minutes, 40 minutes (see [0386]).
Regarding Claim 13, Broughton et al teaches that the system can detect at least 102 copies of the target pathogen nucleic acid (since samples containing either 15,000, 4,000, 1,000, 500, 200, 100, 50, 20, or 0 copies of a SARS-CoV-2 N-gene target nucleic acid were detected) (see [0197]). Furthermore, examiner Wecker notes that claim 13 is an apparatus claims and while features of an apparatus may be recited either structurally or functionally (see In re Schreiber, 128 F.3d 1473, 1478, 44 USPQ2d 1429, 1432 (Fed. Cir. 1997), MPEP 2114), "[A]pparatus claims cover what a device is, not what a device does (or can do)." Hewlett-Packard Co. v. Bausch & Lomb Inc., 909 F.2d 1464, 1469, 15 USPQ2d 1525, 1528 (Fed. Cir. 1990) (emphasis in original). See MPEP 2114.
Regarding Claim 14, Broughton et al teaches that the RPA amplification is isothermal amplification (see [0022], [0049], [0381] and [0433]).
Regarding Claim 16, Broughton et al teaches A method for detecting a pathogen in a sample or a set of samples collected from a subject or subjects with the pathogen nucleic acid detection system of claim 1 (see above rejection), comprising depositing the sample or set of samples in the RPA reaction chamber of the pathogen nucleic acid detection system (i.e. through a sample inlet port) (see [0510]), amplifying the one or more target pathogen nucleic acids to produce RPA amplification products for each sample (see [0049] and [0328]) , opening the valve and passing the RNA amplification products through the valve to the microfluidic chip thus initiating CRISPR/Cas 12a nonspecific cleavage of the cleavable nucleic acid probe (see [0158], [0501], [0526] and [0880]) , and detecting the detectable signal generated in the multiplexed detection chamber wherein the detectable signal indicates presence of the target pathogen nucleic acid and presence of the pathogen in the sample (see [0319]-[0320] and [0326]). In addition, Broughton et al teaches that a positive or negative control can be visualized in the detection region (see [0326], [0429] and [0721]).
Regarding Claim 17, Broughton et al teaches that the subject (i.e. the user) performs the method (see [0319], [0327] and [0524]).
Regarding Claim 18, Broughton et al teaches that the method is completed in less than 60 minutes (see [0327]).
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim 12 is rejected under 35 U.S.C. 103 as being unpatentable over Broughton et al as applied to claim 1 above, and further in view of Zhang et al.
Regarding Claim 12, Broughton et al does not explicitly disclose that the CRISPR/Cas detection reagents include trehalose.
However, in the analogous art of CRISPR systems for Coronavirus diagnostics, Zhang et al teaches systems and methods for rapid diagnostics related to the use of CRISPR effector systems and optimized guide sequences for detection of coronavirus, including multiplex lateral flow diagnostic devices and methods of use (see abstract). In addition, Zhang et al teaches that the system may further incorporate an excipient such as trehalose, histidine or glycine, wherein such excipients aid in rate of reaction, specificity, or other variables (see [0273]). It would have been obvious to one of ordinary skill in the art to modify the system of Broughton et al by incorporating the use of trehalose for the benefit of aiding in rate of reaction and specificity.
Claim 12 is rejected under 35 U.S.C. 103 as being unpatentable over Broughton et al as applied to claim 1 above, and further in view of Pawell et al.
Regarding Claim 12, Broughton et al does not explicitly disclose that the CRISPR/Cas detection reagents include trehalose.
However, in the analogous art of devices for intracellular delivery, Pawell et al teaches that Trehalose was added to the media to enhance cell viability and recovery. Trehalose is commonly used as an excipient and has been demonstrated to reduce cell loss during electroporation (see [0190]).
It would have been obvious to one of ordinary skill in the art to modify the system of Broughton et al by incorporating the use of trehalose for the benefit of enhancing cell viability and recovery, while reducing cell loss during electroporation.
Allowable Subject Matter
Claims 7 and 15 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Regarding Claim 7, the prior art neither teaches nor fairly suggests that the CRISPR/Cas detection reagents include a N gene sgRNA having SEQ ID NO: 3 and a S gene sgRNA having SEQ ID NO:6 and wherein the positive control is a mammalian RNAse P gene with a RNAse P sgRNA having SEQ ID NO: 9.
Regarding Claim 15, the prior art neither teaches nor fairly suggests reagents for RPA amplification comprises a reverse transcriptase, a forward and reverse primer for SARS-CoV-2 N gene having SEQ ID NO:1 and SEQ ID NO:2, respectively, a forward and reverse primer for SARS-CoV-2 S gene having SEQ ID NO:4 and SEQ ID NO: 5, respectively, and optionally that the forward and reverse primer is for human P RNAse gene having SEQ ID NO: and SEQ ID NO:8, respectively.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JENNIFER WECKER whose telephone number is (571)270-1109. The examiner can normally be reached 9:30AM - 6 PM EST M-F.
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/JENNIFER WECKER/ Primary Examiner, Art Unit 1797